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Sulfated alginate as a mimic of sulfated glycosaminoglycans: binding of growth factors and effect on stem cell behavior

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Detalhes bibliográficos
Resumo:Sulfated glycosaminoglycans (GAGs) are principal elements of the extracellular matrix, where they are involved in a plethora of signaling pathways mainly via interactions with diverse proteins such as growth factors and cytokines. However, the mechanisms that drive these interactions are not yet clear, mostly because of the difficulty to access large quantities of homogeneously sulfated natural GAGs. In this work, GAG mimics are synthesized from readily available alginate with different degrees of sulfation (DS, from 0.8 to 2.6) by simple process. The effect of the DS is determined on the binding of basic fibroblast growth factor (FGF-2). The enzyme-linked immunosorbent assay demonstrates that the binding of FGF-2 is significantly greater for alginates with high DS as compared to unmodified and low sulfated analogs. These results are further applied to engineer FGF-2-loaded substrates for stem cell culturing using the layer-by-layer approach. All films support the attachment and growth of adipose derived stem cells (ADSCs). Noteworthy, highly sulfated alginates maintain the stemness of the ADSCs that exhibit remarkably long filopodia. These results can be exploited in the engineering of novel substrates that induce targeted cell behavior via controlled protein delivery and for tissue engineering constructs applicable in various regenerative approaches.
Autores principais:Mhanna, Rami
Outros Autores:Becher, Jana; Schnabelrauch, Matthias; Reis, R. L.; Pashkuleva, I.
Assunto:Alginate Biomimetic materials Growth factors Layer-by-layer Sulfated glycosaminoglycans
Ano:2017
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
Descrição
Resumo:Sulfated glycosaminoglycans (GAGs) are principal elements of the extracellular matrix, where they are involved in a plethora of signaling pathways mainly via interactions with diverse proteins such as growth factors and cytokines. However, the mechanisms that drive these interactions are not yet clear, mostly because of the difficulty to access large quantities of homogeneously sulfated natural GAGs. In this work, GAG mimics are synthesized from readily available alginate with different degrees of sulfation (DS, from 0.8 to 2.6) by simple process. The effect of the DS is determined on the binding of basic fibroblast growth factor (FGF-2). The enzyme-linked immunosorbent assay demonstrates that the binding of FGF-2 is significantly greater for alginates with high DS as compared to unmodified and low sulfated analogs. These results are further applied to engineer FGF-2-loaded substrates for stem cell culturing using the layer-by-layer approach. All films support the attachment and growth of adipose derived stem cells (ADSCs). Noteworthy, highly sulfated alginates maintain the stemness of the ADSCs that exhibit remarkably long filopodia. These results can be exploited in the engineering of novel substrates that induce targeted cell behavior via controlled protein delivery and for tissue engineering constructs applicable in various regenerative approaches.

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